Zinc finger, RING-type (IPR001841)
Short name: Znf_RING
Overlapping homologous superfamilies
- Zinc finger, RING/FYVE/PHD-type (IPR013083)
- Zinc finger, RING-type (IPR001841)
- BARD1, Zinc finger, RING-type (IPR039503)
- Cellulose synthase, RING-type zinc finger (IPR027934)
- E3 ubiquitin-protein ligase CBL-B, RING finger, HC subclass (IPR039520)
- E3 ubiquitin-protein ligase Msl2, zinc RING finger (IPR032043)
- Listerin, zinc finger, RING-type (IPR039804)
- RING finger protein 219, RING finger (IPR035691)
- RING-type zinc-finger, LisH dimerisation motif (IPR027370)
- RNF126, RING finger, H2 subclass (IPR039571)
- Zinc finger, C3HC4 RING-type (IPR018957)
- Zinc finger, RING-H2-type (IPR024766)
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [PMID: 10529348, PMID: 15963892, PMID: 15718139, PMID: 17210253, PMID: 12665246]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few [PMID: 11179890]. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.
This entry represents RING-type zinc finger domains. The RING-finger is a specialised type of Zn-finger of 40 to 60 residues that binds two atoms of zinc, and is probably involved in mediating protein-protein interactions [PMID: 8317827, PMID: 8804826, PMID: 8744354]. There are two different variants, the C3HC4-type and a C3H2C3-type, which are clearly related despite the different cysteine/histidine pattern. The latter type is sometimes referred to as 'RING-H2 finger'. The RING domain is a protein interaction domain that has been implicated in a range of diverse biological processes. E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain. E3 ubiquitin-protein ligases determine the substrate specificity for ubiquitylation and have been classified into HECT and RING-finger families. More recently, however, U-box proteins, which contain a domain (the U box) of about 70 amino acids that is conserved from yeast to humans, have been identified as a new type of E3 [PMID: 12944364]. Various RING fingers also exhibit binding to E2 ubiquitin-conjugating enzymes (Ubc's) [PMID: 10662664, PMID: 10514377, PMID: 10577187].
Several 3D-structures for RING-fingers are known [PMID: 8804826, PMID: 8744354]. The 3D structure of the zinc ligation system is unique to the RING domain and is referred to as the 'cross-brace' motif. The spacing of the cysteines in such a domain is C-x(2)-C-x(9 to 39)-C-x(1 to 3)-H-x(2 to 3)-C-x(2)-C-x(4 to 48)-C-x(2)-C. Metal ligand pairs one and three co-ordinate to bind one zinc ion, whilst pairs two and four bind the second.
Note that in the older literature, some RING-fingers are denoted as LIM-domains. The LIM-domain Zn-finger is a fundamentally different family, albeit with similar Cys-spacing (see IPR001781).